Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions
Abstract
This project is focused on an animal model of the human disease, systemic sclerosis (SSc), called Tsk2/+. The SSc-like traits in Tsk2/+ heterozygotes are highly penetrant. In addition to a readily apparent skin fibrosis resulting from ECM anomalies, Tsk2/+ mice show autoimmune and inflammatory features that closely resemble human SSc features, making it useful as a pre-clinical model. In this report, we show a clear time dependence on the gene expression in the skin of the Tsk2/+ mice. We have pinpointed at least one candidate gene in the interval for Tsk2/+ and have confirmed the sequence difference between Tsk2/+ and the parent strain, 101/H5. We present preliminary results on the expression of TGF mRNA from cells cultured on ECM from Tsk2/+ and WT littermates that suggest a mechanism for the up-regulation of TGF seen in the mutant strain. We show that elastin content in the skin, known to be controlled by TGF 6 and possibly up-regulated in SSc7, is the earliest indicator of tight-skin in the tissue
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA569607
Entities
People
- Elizabeth Blankenhorn
Organizations
- Drexel University